BACKGROUND: Exercise for prostate cancer (PCa) survivors has been shown to be effective in addressing metabolic function and associated co-morbidities, as well as sarcopenia and significant functional impairment resulting from long-term androgen deprivation. Evidence on the cost-effectiveness of exercise interventions for PCa, however, is lacking, thus the aim of this study was to determine the cost-effectiveness of a supervised exercise intervention for long-term PCa survivors who previously received radiation therapy and androgen-deprivation therapy. METHODS: Cost-effectiveness analysis from an Australian healthcare-payer perspective was conducted using patient-level data from a multicentre randomised controlled trial (RCT) of supervised exercise training (resistance and aerobic) compared to receiving printed exercise material and a recommendation to exercise in long-term PCa survivors (> 5 years post-diagnosis). Analysis was undertaken for the 6-month supervised exercise portion of the intervention, which involved 100 men aged between 62 and 85 years, 50 in each arm. The primary outcome was cost per quality-adjusted life-years (QALYs). RESULTS: A 6-month supervised exercise intervention for PCa survivors resulted in an incremental cost-effectiveness ratio of AU$64,235 (2018 AUD) at an incremental cost of AU$546 per person and a QALY gain of 0.0085. At a willingness-to-pay of AU$50,000, the probability that the intervention is cost-effective was 41%. Sensitivity analysis showed that maintenance of benefits via a 6-month home-based intervention, immediately following the supervised intervention, lowered the cost per QALY gained to AU$32,051. DISCUSSION: This is the first cost-effectiveness analysis of exercise for PCa survivors. The intervention was effective, but unlikely to be cost-effective at the generally accepted willingness-to-pay of AU$50,000 per QALY. It is likely that evidence to support cost savings from post-intervention outcomes would reveal greater benefits and contribute to a more comprehensive cost-effectiveness analysis. Future RCTs should incorporate longer follow-up durations and collection of data to support modelling to capture future health benefits. Measures of quality of life or utility more sensitive to the impact of physical activity would also improve future economic evaluations.